Journal of Veterinary Medical Science
Online ISSN : 1347-7439
Print ISSN : 0916-7250
ISSN-L : 0916-7250
Pharmacology
Eukaryotic elongation factor 2 kinase inhibitor, A484954 induced diuresis via nitric oxide production in spontaneously hypertensive rats
Tomoko KODAMAKosuke OTANIMuneyoshi OKADAHideyuki YAMAWAKI
Author information
JOURNAL OPEN ACCESS
Supplementary material

2023 Volume 85 Issue 12 Pages 1314-1318

Details
Abstract

Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a protein kinase that inactivates eEF2, a protein that mediates a peptidyl-tRNA translocation during an elongation step of protein synthesis. We have previously shown that eEF2K was involved in pathogenesis of essential and pulmonary hypertension. A484954 (7-amino-1-cyclopropyl-3-ethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d] pyrimidine-6-carboxamide), a selective eEF2K inhibitor, is a membrane permeable small molecule. We have previously shown that A484954 lowered blood pressure and induced diuretic effects in spontaneously hypertensive rats (SHR) due to an increase in renal blood flow. Here we aimed to reveal mechanisms underlying the diuretic effects of A484954 in SHR. A484954-induced diuresis and increase in urinary Na+ excretion were inhibited by N (G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor. A484954 increased mRNA expression of angiotensin type 2 receptor (AT2R) and nuclear factor-erythroid 2-related factor 2 (Nrf2). In summary, we for the first time revealed that A484954 induces diuresis in SHR at least partly via the activation of NO/Nrf2/AT2R pathway.

Content from these authors
© 2023 by the Japanese Society of Veterinary Science

This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license.
https://creativecommons.org/licenses/by-nc-nd/4.0/
Previous article Next article
feedback
Top